EPSTEIN-BARR-VIRUS LATENT MEMBRANE PROTEIN-1 ONCOGENE DELETION IN POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is a multifu nctional oncoprotein, A 30-bp deletion of the 3' end of the LMP1 gene (del-LMP1) has been identified in some EBV isolates, This deleted LMP1 gene encodes a protein, altered on the carboxy terminus, which is tho ught to have greater oncogenic potential than the mild type. Recently, it was suggested that del-LMP1 plays a role in the development of mal ignant lymphomas occurring in immunocompromised patients, To further e lucidate the role of del-LMP1 in post-transplantation lymphoproliferat ive disorders (PT-LPDs) we analyzed 58 PT-LPD lesions from 36 heart an d kidney organ transplant recipients, Overall, del-LMP1 was detected i n 44% of the cases, Four plasmacytic hyperplasias (36%), eight polymor phic B-cell hyperplasias/polymorphic B-cell lymphomas (38%), and five malignant lymphomas/multiple myelomas (71%) exhibited del-LMP1. Two of the three patients displaying disease progression showed wild-type LM P1 gene (w-LMP1) and one showed del-LMP1. LMP1 status remained the sam e in all three patients during disease progression, In patients underg oing biopsy of multiple separate PT-LPD lesions representing different clonal lymphoid proliferations, LMP1 status was the same in all of th e lesions in each patient, Furthermore, although the polyclonal lesion s harbor multiple EBV infectious events, they either showed w- or del- LMP1 but not both, Analysis of the tissues without an apparent PT-LPD (peripheral blood, bone marrow, or colon) revealed EBV and LMP1 type i dentical to that found in the lesions, In conclusion, the presence or absence of del-LMP1 in PT-LPDs does not correlate with the histopathol ogical category or the malignant nature of the lymphoid proliferation, LMP1 status does not change during disease progression and is the sam e within multiple lesions occurring in the same patient regardless of their clonal relationship, These findings suggest that 1) EBV infectio n in patients with PT-LPDs occurs with aw-or del-LMP1-type EBV isolate and does not change once a patient acquires the virus and 2) the infe ction is an early event in the development of PT-LPDs and transformati on is induced regardless of the type of LMP1.